Kmt2c/Mll3 Haploinsufficiency Causes Autism-like Behavioral Deficits in Mice.

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• KMT2C (histone lysine N-methyltransferase 2C) is a high-risk gene for autism spectrum disorder (ASD).
• The precise causal link between KMT2C haploinsufficiency and ASD remains unclear.
• KMT2C plays critical roles in neurodevelopment, with expression peaking during brain development.

Purpose of the Study:

• To investigate the impact of germline Kmt2c haploinsufficiency on autism-like behaviors in a mouse model.
• To establish a causal link between KMT2C haploinsufficiency and ASD-associated behavioral deficits.

Main Methods:

• Generation of Kmt2c haploinsufficiency mice to model human KMT2C variants.
• Behavioral assessments including motor function, anxiety, social interaction, self-grooming, novel object recognition, and spatial memory tests.
• Comparison of Kmt2c haploinsufficiency mice with Kmt2c(+/+) controls.

Main Results:

• Kmt2c haploinsufficiency mice exhibited autism-like social deficits and increased self-grooming in both sexes.
• Deficits in novel object recognition and spatial memory were observed in Kmt2c haploinsufficiency mice.
• No significant motor or anxiety-like behavioral deficits were found.

Conclusions:

• Germline Kmt2c haploinsufficiency causes core ASD-like behavioral deficits in mice.
• These findings reveal a causal link between Kmt2c haploinsufficiency and ASD-like behaviors.
• Kmt2c haploinsufficiency mouse models are valuable for studying ASD mechanisms and developing therapies.